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Six1 Protein Regulates The Mechanism Of Proliferative Metastasis Of Osteosarcoma

Posted on:2018-06-16Degree:DoctorType:Dissertation
Country:ChinaCandidate:L M ChaoFull Text:PDF
GTID:1364330548988214Subject:Surgery
Abstract/Summary:PDF Full Text Request
Osteosarcoma is a malignant tumor originating from the interosseous tissue,accounting for 30%of the primary malignant bone tumor,among young people was between 10 and 25 years old,and the incidence is the third place in tumors.Because of its high degree of malignancy,it is easily prone to lung metastasis in early tme,of which about 10-20%of patients were found lung metastases and poor prognosis,the current treatment is amputation,although with the Targeted chemotherapeutic drugs are widely used,the survival rate has increased,but because of the resistance rate,the average survival time of patients with osteosarcoma less than 5 years.Therefore,it is a great challenge and demand to find the intervention target for osteosarcoma progress and drug resistance.In the pathology of osteosarcoma,the continuous advance of its pathological manifestations is:osteosarcoma cells continue to proliferate and eventually lead to the metastasis.It can be seen that the proliferation and metastasis of osteosarcoma cells are important event leading to its pathological progress.There are no effective means to prevent its progress.Therefore,in order to reduce the mortality of osteosarcoma,we need to analysis the continuous development of osteosarcoma mechanism and to seek a new effective intervention strategy.However,the molecular mechanism of osteosarcoma proliferation and metastasis is unclear.Multiple activation of multiple signaling pathways,inhibition of apoptosis signaling pathways and changes in malignant microenvironment of tumor are the basis of proliferation and metastasis of osteosarcoma.At present,a large number of studies has support that EGFR-mediated signaling pathway is risk factors leading to the progress of osteosarcoma,although the EGFR mutation of targeted drugs in clinical work has achieved a certain effect,but some patients quickly resistant andResulting in an average survival less than 5 years.With the continuous development of genomics research,through the way to screening of osteosarcoma mutant genes,we found that the mutation of SIX1 gene is the core of osteosarcoma pathology progress.Relevant evidence suggests that SIX1 gene mutations are associated with KRAS,EGFR,PIK3CA which were known oncogene and have significant correlations with apoptosis proteins and malignant microenvironment of osteosarcoma.Thus we speculate that SIX1 may be an important intervention for promoting tumor metastasis,inhibiting apoptosis and altering the malignant environment of osteosarcoma!We propose scientific hypotheses:what is regulate the activation of multiple proliferative signaling pathways,suppress the apoptosis signaling pathway,and change the malignant microenvironment during the progression of osteosarcoma pathology?Can we find common interventions to control their activity?However,these are unresolved scientific issues.To solve the above scientific problems,we used pcDNA transacted osteosarcoma cells to up-regulate the expression of SIX1 protein and SIX1 siRNA interference technique to down-regulate the expression of SIX1 protein and observe the expression of SIX1 protein in osteosarcoma.On the basis of this innovative work,the molecular mechanism of the pathology of osteosarcoma was further analyzed by over expression and low expression of SIX1 protein in osteosarcoma cells.The clinical data were gathered and analyzed.The prevention and treatment will provide new research ideas and intervention strategies for osteosarcoma.
Keywords/Search Tags:osteosarcoma, SIX, EGFR, multiplication, apoptosis
PDF Full Text Request
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